Heparin-induced thrombocytopenia

Summary

Heparin-induced thrombocytopenia (HIT), typically occurring in the second week of heparin therapy, is an antibody-mediated adverse drug reaction associated with increased thrombotic risk. The most important antigens are located on platelet factor 4 (PF4)/heparin complexes. HIT is always caused by platelet-activating antibodies, but not all PF4/heparin-reactive antibodies cause HIT. Thus, tests have a high negative, but only a moderate, positive predictive value. Clinical suspicion of HIT requires cessation of heparin and substitution with an alternative anticoagulant. As these drugs have an increased bleeding risk, they should be used in therapeutic doses only if HIT is considered very likely. Avoiding/postponing coumarin is crucial in minimizing microthrombotic complications. Recent studies of HIT immunobiology suggest that HIT mimics immunity against repetitive antigens, as are relevant in microbial defense. Thus, understanding HIT may help unravel why host defenses can trigger autoimmunity.

Zusammenfassung

Die Heparin-induzierte Thrombozytopenie (HIT) ist eine Antikörper-vermittelte, unerwünschte Arzneimittelreaktion, die mit einem erhöhten Risiko für thromboembolische Komplikationen verbunden ist. Die HIT tritt typischerweise in der zweiten Woche der Heparingabe auf. Das wichtigste Antigen ist der Komplex zwischen dem Chemokin Plättchenfaktor 4 (PF4) und Heparin. Die HIT wird immer durch Thrombozyten-aktivierende Antikörper induziert, aber nicht alle PF4/Heparin-Antikörper induzieren eine HIT. Daher haben alle Laborteste einen hohen negativ-prädiktiven Wert, aber nur einen eingeschränkt positiv-prädiktiven Wert.

Der klinische Verdacht auf HIT erfordert die Beendigung der Heparingabe und die Antikoagulation mit alternativen Antikoagulanzien. Da diese oft mit einem erhöhten Blutungsrisiko verbunden sind, sollten sie nur dann in therapeutischer Dosierung gegeben werden, wenn die HIT eine sehr wahrscheinliche Ursache eines Abfalls der Thrombozytenwerte ist. Durch die Vermeidung von Vitamin-K-Antagonisten in der Akutphase der HIT kann das Risiko von mikrovaskulären Gefäßverschlüssen bei HIT wesentlich reduziert werden. Aktuelle Untersuchungen zur Pathophysiologie der HIT weisen darauf hin, dass die HIT durch Immunreaktionen gegen repetitive Antigenstrukturen verursacht wird, wie sie ansonsten vor allem für die Bakterienabwehr von Bedeutung sind. Das weitere Verständnis der Immunologie der HIT kann beitragen, den Zusammenhang zwischen bakteriellen bzw. viralen Infektionen und der Induktion von Autoimmunerkrankungen besser zu verstehen.

Keywords

Heparin - heparin-induced thrombocytopenia - platelets - pathogenesis - immunology - anticoagulants

Schlüsselwörter

Heparin - Heparin-induzierte Thrombozytopenie - Thrombozyten - Pathogenese - Immunologie - Antikoagulanzien

• References

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